JP2015535823A - Biological synthesis process of nano arsenic trioxide and its use in the treatment of diseases including cancer - Google Patents

Abstract

The present invention relates to novel nano arsenic trioxide, buttermilk, goat urine, dolicos bean, and ginger, bitter gourd, and, as defined by its low toxicity, higher bioavailability, and nanoparticle size It is a biological synthesis process using several other plant materials such as bananas. The present invention purifies the raw form of arsenic trioxide by boiling with buttermilk, goat urine, and Drichos bean extract in subsequent steps, followed by biological steps in subsequent steps. Is carried out in various steps, including grinding the chemically purified arsenic trioxide with ginger and bitter gourd extracts, and heating the dried product obtained after grinding with bananas. Leading to the production of nano arsenic trioxide. The novel products described above are effective in the treatment of various diseases, including various types of cancer in animals and humans. The novel nano arsenic trioxide obtained through the process of the present invention is less toxic and has a higher bioavailability. Its applicability extends to multiple plant treatments, agriculture, nanotechnology, and other areas where arsenic trioxide can be used.

Description

  The present invention is a novel process for producing nano arsenic trioxide using multiple plant materials, buttermilk, and goat urine. This process is environmentally friendly. The novel products obtained through the process of the present invention are more biologically available and can be used in a variety of ways, including but not limited to leukemia, other types of malignant and benign tumors, rheumatism. It is more effective in the treatment of diseases. The products of the present invention are also applied in agriculture, horticulture, veterinary therapy, and several other fields known to those skilled in the art that arsenic trioxide may be used.

The applicability of arsenic minerals has long been known in traditional Chinese and Indian medicine. In the 18th century Thomas Fowler prepared a solution of arsenic trioxide (As ₂ O ₃ ) based on potassium bicarbonate, which would be known as a Fowler solution. The 18th century pharmacology text shows the use of arsenic paste for the treatment of various diseases including cancer (Karen H. Antman; Introduction: The history of arsenic trioxide in cancer therapy; The Oncologist 2001; 6 ( suppl 2): 1-2). In the 1990s, Chinese researchers reported that a mixture of herbs containing arsenic trioxide could induce complete recovery in patients suffering from acute promyelocytic leukemia. (Dan Douer, Wendy Hu et. Al .; Arsenic trioxide (Trisenox) Therapy for Acute Promyelocytic Leukaemia in the setting of hematopoietic stem cell transplantation .; The Oncologist 2003; 8: 132-140)

  Arsenic is widely present in nature in its trivalent and pentavalent forms. The toxicity of arsenic depends strongly on its chemical form. In Indian and Chinese traditional medicine, three forms of minerals of arsenic, ie stone yellow, poultry stone, and arsenite, are used alone and with other minerals to treat various diseases. ing. The nature of these arsenic compounds in the body depends on various major factors, including solubility, absorption, distribution, and excretion. Although arsenic trioxide is the most biologically available, it is very toxic compared to stone yellow and chicken stone. Chicken crown stone is also the main ingredient in bhasma of Indian Ayurvedic medicine. Chicken crown stone is used for both external medicine and internal medicine. Arsenic trioxide obtained after purification of arsenite has short-term toxicity. For this reason, its application to therapy is of great concern. To increase the application of chicken crown stone treatment, chicken crown stone nanoparticles are prepared by cryogrinding with polyvinylpyrrolidone and sodium dodecyl sulfate. (Jie Liu et. Al., Mineral Arsenicals in Traditional Medicines: Orpiment, Realgar, and Arsenolite, The Journal of Pharmacology and experimental therapeutics, Vol. 326, No.2, pg. 363-368, 2008)

  Prior art studies have shown that arsenic trioxide has and has been used to treat cancer. European Patent Application No. 2374463, European Patent No. 2394702, European Patent Application No. 1526216, International Publication No. 9924029, US Pat. No. 6,884,439, US Patent US Pat. No. 6,855,339, US Pat. No. 6,982,096, US Pat. No. 6,723,351, US Pat. No. 6,720,011 It is the result of a prior art search showing the use of arsenic oxide. However, the present invention is unique from the standpoint of the preparation process, and the novel nanoarsenic trioxide obtained through the process of the present invention generally ranges in particle size from 10 nm to 1000 nm. Furthermore, the new products are chemically more stable and are more bioavailable and safe due to their lower toxicity for therapeutic administration to humans, animals, and plants. Prior art processes for producing arsenic trioxide used for therapeutic applications include the purification of arsenic trioxide through a chemical process. The present invention purifies arsenic trioxide through biological synthesis.

  The present invention relates to the production of novel nanoarsenic trioxide by a novel process. This process involves purification to make nano-arsenic trioxide chemically more stable and reduce the particle size of arsenic trioxide with multiple plant materials, buttermilk, and goat urine. The plurality of plant materials used in the process of the present application are Dolichos biflorous, bitter gourd (Momordica charantia), ginger (Zingiber officinale), and banana (Musa paradisica). The scope of the present invention also includes a plurality of plant materials, buttermilk, goat urine, or cellulose described herein for the purposes of the process of the invention and the production of novel products, It also includes the use of multiple active ingredients found in other plants, organic or inorganic materials with similar properties and chemistry, as known to those skilled in the art.

  Buttermilk is a fermented milk product obtained from bovine milk. The sour taste of buttermilk is due to the presence of lactic acid. The pH level of buttermilk is generally accepted as 4.41 to 4.84. Buttermilk can also be made through traditional processes, through the cultivation and milk acidification processes. One stage of the present invention involves the purification of arsenic trioxide using buttermilk. The use of buttermilk is one embodiment of the present invention, as it is replaced by any other fermented form of milk, either obtained through traditional methods or cultured. If there is, it is possible to derive the same result. Replaces fermented milk obtained or cultured through traditional methods with chemically produced fermented milk or with multiple active ingredients induced with the same effect known to those skilled in the art It cannot be excluded.

  Goat and cattle urine is a component in Indian Ayurvedic medicine and other traditional Indian medicine. Goat urine is used to treat tuberculosis by tribes in the Western Ghats of India (P. Padmanabhan & KA Sujana, 2008, Animal products in traditional medicine from Attapady hills of Western Ghats, Indian Journal of Traditional Medicine, Vol.7 (2), pg.326-329). However, the use of goat urine in the present process is neither traditional knowledge nor expected.

  The pharmacological effects of several plant materials belonging to the genus Zingiber and family Zingiberaceae are well known in traditional medicine. Ginger is a plant species of the genus Ginger. Ginger (Zingiber Officinale), Ginger rhizome is one of the most widely used ginger species in the family Ginger, and is known for its medical use in traditional Chinese and Indian medicine. Ginger has a number of active ingredients such as sesquiterpene hydrocarbons, mainly gingiverene, active gingerol, gingerone, and paradol that can be converted to gingerol. 6-Gingerol and 6-shogaol have shown pharmacological activity in the treatment of nausea induced by chemotherapy, including antipyretic and analgesic effects (Monograph, Alternative Medicine Review, Volume 8, No. 3, 2003, pg. 331-335). However, the use of extracts of ginger or ginger plant materials for the reduction of metalloid particle size is not known. The process of the present invention also includes reducing the particle size of arsenic trioxide to nanoparticles using ginger.

  Bitter Melon (Momordica charantia, Bitter Melon) is a tropical vegetable of the family Cucurbitaceae. It is a flowering vine with multiple known medicinal properties. The fruit contains glycosides, saponins, alkaloids, reducing sugars, resins, multiple phenolic components, fixed oils, and free acids. The chemical components of bitter gourd are alkaloids, charantin, charine, cryptoxanthine, cucurbitine, cucurbitacins, cucurbitans, cycloartenols, diosgenin, eleostearic acids, erythrodiol, galacturonic acids, Gentisic acid, goyaglycosides, goyasaponins, guanylate cyclase inhibitors, gypsogenin, hydroxytryptamines, caronidiols, lanosterol, lauric acid, linoleic acid, linolenic acid, momorcharasides, momorcharins , Momordenol, momordicillin, momordicin, momordicinin, momordicoside, momordin, momordolo, multiflorenol, myristic acid, nerolidol, oleanol , Oleic acid, oxalic acid, pentadecanes, peptides, petrothelic acid, polypeptides, proteins, ribosome inactivating proteins, rosmarinic acid, rubixanthine, spinasterol, steroidal glycosides, stigmasterdiol (Stigmasta-diol), stigmasterol, taraxerol, trehalose, trypsin inhibitor, uracil, vacine, v-insulin, verbascoside, bicine, zeatin, zeatin riboside, zeaxanthin, zeinoxanthine amino acid-aspartic acid, serine , Glutamic acid, thscinne, alanine, g-aminobutyric acid and pipecolic acid, ascorbigen, b-sitosterol-d-glucoside, citrulline, elastolol, flavochrome, lutein, lycopene, pipecolic acid

  Banana (Musa paradisica) is a herbaceous plant of the genus Musa. The old scientific name Musa paradisica is rarely used due to the emergence of multiple hybrids. At present, this species is referred to as Musa acuminata or Musa balbisiana or triploid hybrid. Fruit has a pharmacological effect as well as several plant materials. In the present invention, an extract of plant material is used.

  Doricos bean is commonly used as an astringent, diuretic, and tonic. A number of enzymes found in Dorico peas have been identified as urease, allantoinase, ribonuclease, nicotinamide deaminase, bn-acetylglucosaminidase, a and b galactosidase, a-mannosidase and b-glucosidase.

  In order to increase the therapeutic applicability and bioavailability of arsenic trioxide, the present invention comprises a process of boiling, grinding and heating with multiple plant materials, buttermilk, and goat urine. Purify commercially available arsenic trioxide through biological purification. Briefly, arsenic trioxide, which is available in the market and in its unprocessed form, is passed through a purification process by boiling with buttermilk, goat urine, and dorikome beans in successive steps. . The purified arsenic trioxide, together with taxonomic genus Momordica plant material extract and taxonomic ginger rhizome extract, helps reduce particle size through the grinding process. Passed. The product obtained by grinding is then heated with an extract of the plant material of the genus Bacillus. The heating process is carried out in a closed container to collect the sublimated product. The product collected from inside the container lid is a novel nano-arsenic trioxide with high therapeutic value and solubility. Furthermore, the bioavailability and therapeutic applicability of the novel product nano-arsenic trioxide obtained through the process of this invention is higher due to its lower toxicity and particle size. is there.

  The raw powder form of arsenic trioxide available on the market is biologically purified using aqueous extracts of buttermilk, goat urine, and dorikos bean in various steps, as follows: Grinding and heating continues.

  Step 1: Arsenic trioxide in coarse powder form is submerged in an earthenware containing boiling buttermilk. Arsenic trioxide is hung so as to sink into boiling buttermilk without touching the side of the earthenware. This process is carried out for 7 hours. Arsenic trioxide must always be submerged during the boiling process. Therefore, buttermilk would have to be added repeatedly during the boiling process in order to keep the arsenic trioxide submerged throughout.

  Step 2: After boiling arsenic trioxide with buttermilk according to step 1, it is suspended and submerged in boiling goat urine contained in an earthenware so as not to touch the side of the container. This process is carried out for 7 hours. Also during this step, arsenic trioxide should be kept submerged throughout the entire period of boiling with the goat urine. Therefore, it may be necessary to add goat urine during this process to maintain the arsenic trioxide in the submerged state.

  Step 3: After boiling arsenic trioxide with goat's urine according to step 2, then hang it up and touch the side of the container so that it does not touch the side of the container Sink inside. This process is carried out for 7 hours. Similar to the previous steps, it was necessary to repeatedly add the aqueous extract of Doricosm beans throughout the boiling to keep the arsenic trioxide completely submerged.

  The process duration of 7 hours given in steps 1 to 3 cannot be considered a limitation. In this process, arsenic trioxide can be suspended using cotton yarn or with multiple materials of similar properties. The container used can be a ceramic container or any container with similar properties that would be known to those skilled in the art. The product is a pale yellow powder. Biological variations that would occur in goat urine, buttermilk, and extracts of multiple plant materials are anticipated in the present invention. The same is true if arsenic trioxide is passed through steps 1, 2, or 3 in a different order such that step 3 or step 2 can be performed as step 1 or vice versa. As the results are possible, the scope of the present invention also predicts that the order of use of the extract of buttermilk, goat urine and dolicos bean can be interchanged.

  Step 4: The product of Step 3 is ground for 7 hours with the extract of bitter gourd. Grinding time cannot be considered a limitation. The grinding process is repeated three times in succession. That is, once the product of grinding is completely dry, the next grinding is started. Generally, it takes 7 hours for the mixture to dry. However, since how many hours depends on the amount of material, 7 hours cannot be regarded as a limitation.

  Step 5: The product of Step 4 is ground for 7 hours with ginger, ginger rhizome extract. Grinding time cannot be considered a limitation. Similar to step 4, the grinding is performed three times in succession. There, the dried product obtained after grinding is further ground with ginger rhizome extract until dry.

  The time given for grinding, i.e. 7 hours, cannot be regarded as a limitation. The desired result is obtained even if grinding is carried out for shorter or longer times. The particle size of the product will vary depending on how long the milling takes. When milling is performed with a mixture of plant materials identified in steps 4 and 5, or its active ingredients, or other organic or inorganic materials with similar properties The possibility of obtaining the desired result is within the scope of the invention. The resulting product color is generally yellowish white.

  Step 6: The product of Step 5 is heated with an extract of banana (Musa paradisica) stems in a closed ceramic container with a removable lid. The volume ratio of product to banana stem extract is preferably 1:10. Heating is carried out stepwise for 12 hours. The duration of heating cannot be considered a limitation. The sublimated product inside the container lid is the final product. The color of this final product is generally a slightly yellowish white. The maximum temperature experienced by the process of the present application is about 500 degrees Celsius. However, the temperature of heating cannot be considered a limitation because desirable results are obtained even below or above 500 degrees Celsius. The temperature at which the product is obtained will vary with the amount of raw arsenic trioxide and several other components.

  The container or apparatus for performing the process of the present application is an earthenware with a removable lid, or any other container known to those skilled in the art to produce similar results.

  The plurality of components in the plurality of steps described above is one embodiment of the present invention. The scope of the present invention also includes organic and inorganic active ingredients of plant and other materials used in the process, or similar properties or chemical properties, containing cellulose, Those skilled in the art know that in this new process for the production of nano arsenic trioxide, the substitution of buttermilk, goat urine, dolicos bean, bitter gourd, ginger, banana, or several other supplements has the desired effect. In addition, a plurality of other plant materials and a plurality of organic substances or inorganic substances are also included.

  The administration of this chemically more stable and novel nano arsenic trioxide obtained through the process of the present invention should be administered as such or in combination with other minerals, metals, chemical elements or compounds. Can do. Both in vitro and in vivo administration is possible with this novel nanoarsenic trioxide. Oral administration of the product can be in conjunction with honey or water, or any other suitable carrier. Dosages can range from 0.01 mg / kg body weight to 10 mg / kg body weight. Depending on the nature of the disease, it can be administered daily. In the case of cancer, the duration of administration can in some cases be until complete recovery or tumor reduction.

  The dosage form can be a powder, tablet, capsule, caplet, foam, fluid, jelly, granule, or any other palatable administrable form.

  Nano-arsenic trioxide obtained through this process, which generally varies in size from 10 nm to 1000 nm, is also used in nutritional supplements, herbal and mineral compositions as well as pharmaceutical or other therapeutic compositions Can also be done.

  The products of the process of the invention are also effective in the treatment of malignant tumors such as malignant and benign cancers, promyelocytic leukemias, other types of leukemias, lymphomas, lung cancers, liver cancers and other solid tumors. is there. This application of nano arsenic trioxide is not limited to only against various cancers, but also includes other degenerative diseases and metabolic abnormalities of important organs such as lung, liver, brain, kidney and the like. This has broad applicability in cancerous diseases of the nervous system, and in particular, but not limited to, multiple multiple infectious disorders that are antibiotic-resistant or antimicrobial-resistant infections such as tuberculosis. Have. This novel arsenic trioxide had a special effect on various enzyme and hormone activities in the body in the treatment of multiple diseases including but not limited to diabetes. This has had special effects at the epiphyseal level, including generally bone development and the prevention and treatment of osteosarcoma and several other types of cancer. Use of this novel product in the treatment of multiple animals, plants, herbs, or other flora, and industrial applications in dietary supplements, cosmetics, herbs, minerals, and other compositions Is predicted.

  The following are some examples. However, the examples given below are not to be considered as limiting with respect to the scope, implementation or use of the invention.

＊量は、ラクトース一水和物により求められた。 Multiple examples of preparations

* Amount was determined by lactose monohydrate.

  The yield of biologically purified nano-arsenic trioxide depends on the amount of raw form of arsenic trioxide used in the process of the present invention. For example, if 100 gm of untreated arsenic trioxide is used in the process of the present invention, the yield of biologically purified and therapeutically effective arsenic trioxide will be in the range of 75-80 gm. Further, the amount will vary depending on the quality of the raw arsenic trioxide used in the process.

Claims (12)

Immersing and boiling arsenic trioxide in untreated powder form in buttermilk, goat urine, and in an aqueous extract of Doricosm beans;
Subsequently, pulverizing the arsenic trioxide obtained after the boiling together with an extract of the plant material bitter gourd until dry,
Further grinding the dried product with ginger extract to dryness;
Subsequently, heating the product obtained after the grinding with a banana extract in a device having a lid;
Collecting nano-arsenic trioxide, a sublimated product, from the inside of the lid;
Having a process.   A product obtained through the process of claim 1.   A plurality of extracts of buttermilk, goat urine, and doricos bean, with multiple active ingredients thereof, or multiple plants containing cellulose, similar to buttermilk, goat urine, and dolicos bean extract The process according to claim 1, wherein the process is carried out by substituting with a plurality of other organic or inorganic materials having the following properties and chemistry.   Nigori is an extract of a plurality of plant materials belonging to the taxonomy of the genus Vulgaris, a plurality of active ingredients thereof, or a plurality of other substances having a plurality of characteristics and chemical properties similar to that of a bitter melon, containing cellulose. The process according to claim 1 or 3, wherein the process is carried out by substitution with a plant material, other organic or inorganic substances.   Ginger is a group of plant materials belonging to the taxonomic family of ginger or rhizomes of other plants with tubers, combinations thereof, their active ingredients, or multiples similar to ginger that contain cellulose The process according to any one of claims 1, 3, and 4, wherein the process is carried out by substituting with a plant material having other characteristics and chemical properties, other organic substances or inorganic substances.   Bananas are taxonomic plants belonging to the genus Baxus, or multiple active ingredients thereof, or cellulose, and other plants with multiple characteristics and chemical properties similar to bananas 6. The process according to any one of claims 1, 3 to 5, wherein the process is replaced by a material, a plurality of organic or inorganic substances.   Claims consisting of dosages ranging from 0.01 mg / kg to 10 mg / kg per body weight for therapeutic use, in any palatable or administrable form in vitro or in vivo in humans and animals Item 7. Use of the nano arsenic trioxide obtained through the process according to any one of Items 1, 3 to 6.   7. The nano-arsenic trioxide obtained through the process according to any one of claims 1, 3 to 6 in a dosage form suitable for the treatment of a plurality of herbs, a plurality of plants and other plant groups. use.   Use of said nano-arsenic trioxide obtained through the process according to any one of claims 1, 3 to 6 in nanotechnology, material science, agriculture, biotechnology and other applicable fields .   7. The pharmaceutical composition, other therapeutic composition, dietary supplement, herbal composition, cosmetic composition, or mineral composition obtained through the process according to any one of claims 1, 3 to 6 Use of nano arsenic trioxide.   7. The nano-arsenic trioxide obtained through the process according to any one of claims 1, 3 to 6 for use defined by its low toxicity, bioavailability and nanoparticle size. application.   7. Any palatable and well-administerable dosage form of the product obtained through the process of any one of claims 1, 3 to 6.